APL Bioengineering最新文献

{"title":"Generation of direct current electrical fields as regenerative therapy for spinal cord injury: A review.","authors":"Lukas Matter, Bruce Harland, Brad Raos, Darren Svirskis, Maria Asplund","doi":"10.1063/5.0152669","DOIUrl":"10.1063/5.0152669","url":null,"abstract":"<p><p>Electrical stimulation (ES) shows promise as a therapy to promote recovery and regeneration after spinal cord injury. ES therapy establishes beneficial electric fields (EFs) and has been investigated in numerous studies, which date back nearly a century. In this review, we discuss the various engineering approaches available to generate regenerative EFs through direct current electrical stimulation and very low frequency electrical stimulation. We highlight the electrode-tissue interface, which is important for the appropriate choice of electrode material and stimulator circuitry. We discuss how to best estimate and control the generated field, which is an important measure for comparability of studies. Finally, we assess the methods used in these studies to measure functional recovery after the injury and treatment. This work reviews studies in the field of ES therapy with the goal of supporting decisions regarding best stimulation strategy and recovery assessment for future work.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41147815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnetic force-based cell manipulation for <i>in vitro</i> tissue engineering.","authors":"Huiqian Hu,&nbsp;L Krishaa,&nbsp;Eliza Li Shan Fong","doi":"10.1063/5.0138732","DOIUrl":"10.1063/5.0138732","url":null,"abstract":"<p><p>Cell manipulation techniques such as those based on three-dimensional (3D) bioprinting and microfluidic systems have recently been developed to reconstruct complex 3D tissue structures <i>in vitro</i>. Compared to these technologies, magnetic force-based cell manipulation is a simpler, scaffold- and label-free method that minimally affects cell viability and can rapidly manipulate cells into 3D tissue constructs. As such, there is increasing interest in leveraging this technology for cell assembly in tissue engineering. Cell manipulation using magnetic forces primarily involves two key approaches. The first method, positive magnetophoresis, uses magnetic nanoparticles (MNPs) which are either attached to the cell surface or integrated within the cell. These MNPs enable the deliberate positioning of cells into designated configurations when an external magnetic field is applied. The second method, known as negative magnetophoresis, manipulates diamagnetic entities, such as cells, in a paramagnetic environment using an external magnetic field. Unlike the first method, this technique does not require the use of MNPs for cell manipulation. Instead, it leverages the magnetic field and the motion of paramagnetic agents like paramagnetic salts (Gadobutrol, MnCl₂, etc.) to propel cells toward the field minimum, resulting in the assembly of cells into the desired geometrical arrangement. In this Review, we will first describe the major approaches used to assemble cells <i>in vitro</i>-3D bioprinting and microfluidics-based platforms-and then discuss the use of magnetic forces for cell manipulation. Finally, we will highlight recent research in which these magnetic force-based approaches have been applied and outline challenges to mature this technology for <i>in vitro</i> tissue engineering.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41172466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human gut epithelium features recapitulated in MINERVA 2.0 millifluidic organ-on-a-chip device.","authors":"Francesca Donnaloja,&nbsp;Luca Izzo,&nbsp;Marzia Campanile,&nbsp;Simone Perottoni,&nbsp;Lucia Boeri,&nbsp;Francesca Fanizza,&nbsp;Lorenzo Sardelli,&nbsp;Emanuela Jacchetti,&nbsp;Manuela T Raimondi,&nbsp;Laura Di Rito,&nbsp;Ilaria Craparotta,&nbsp;Marco Bolis,&nbsp;Carmen Giordano,&nbsp;Diego Albani","doi":"10.1063/5.0144862","DOIUrl":"https://doi.org/10.1063/5.0144862","url":null,"abstract":"<p><p>We developed an innovative millifluidic organ-on-a-chip device, named MINERVA 2.0, that is optically accessible and suitable to serial connection. In the present work, we evaluated MINERVA 2.0 as millifluidic gut epithelium-on-a-chip by using computational modeling and biological assessment. We also tested MINERVA 2.0 in a serially connected configuration prodromal to address the complexity of multiorgan interaction. Once cultured under perfusion in our device, human gut immortalized Caco-2 epithelial cells were able to survive at least up to 7 days and form a three-dimensional layer with detectable tight junctions (occludin and zonulin-1 positive). Functional layer development was supported by measurable trans-epithelial resistance and FITC-dextran permeability regulation, together with mucin-2 expression. The dynamic culturing led to a specific transcriptomic profile, assessed by RNASeq, with a total of 524 dysregulated transcripts (191 upregulated and 333 downregulated) between static and dynamic condition. Overall, the collected results suggest that our gut-on-a-chip millifluidic model displays key gut epithelium features and, thanks to its modular design, may be the basis to build a customizable multiorgan-on-a-chip platform.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41160154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"All-in-one properties of an anticancer-covered airway stent for the prevention of malignant central airway obstruction.","authors":"Zhaonan Li,&nbsp;Wenguang Zhang,&nbsp;Dechao Jiao,&nbsp;Chuan Tian,&nbsp;Kaihao Xu,&nbsp;Haidong Zhu,&nbsp;Xinwei Han","doi":"10.1063/5.0157341","DOIUrl":"10.1063/5.0157341","url":null,"abstract":"<p><p>Malignant central airway obstruction (MCAO) resulting from tumor metastasis and compression severely impairs respiration, posing life-threatening risks. To address this, we employed a synergistic modification strategy, combining cisplatin (CIS) and silver nanoparticles (AgNPs). Polycaprolactone (PCL) served as a drug carrier, enabling the preparation of a functional CIS@AgNPs@PCL fiber membrane-covered airway stent via electrospinning. This approach aimed to enhance the patency rate of MCAO. Characterization via ATR-FTIR, scanning electron microscope-energy-dispersive spectroscopy, and transmission electron microscope confirmed successful immobilization of CIS and AgNPs onto the stent surface. CIS@AgNPs@PCL substantially suppressed non-small cell lung cancer cells (A549), causing DNA damage, ultrastructural disruption, and over 50% apoptosis in 48 h. It also displayed potent antibacterial activity against <i>Staphylococcus aureus</i>, <i>Pseudomonas aeruginosa</i>, and <i>Candida albicans</i> biofilms. A mouse subcutaneous tumor recurrence model assessed anti-cancer efficacy. CIS@AgNPs@PCL fiber-covered stents significantly inhibited lung cancer tissue and enhanced anti-cancer effects by up-regulating caspase-3 and Bax, while down-regulating Bcl-2. This study's functional airway stent provides a proof-of-concept for an integrated anti-cancer and antibacterial strategy. It promptly restores the lumen, inhibits biofilm formation, prevents tumor progression, and improves postoperative MCAO patency.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10503995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10652402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magneto-responsive hyaluronan hydrogel for hyperthermia and bioprinting: Magnetic, rheological properties and biocompatibility.","authors":"L Vítková, N Kazantseva, L Musilová, P Smolka, K Valášková, K Kocourková, M Humeník, A Minařík, P Humpolíček, A Mráček, I Smolková","doi":"10.1063/5.0147181","DOIUrl":"10.1063/5.0147181","url":null,"abstract":"<p><p>Magneto-responsive soft hydrogels are used for a number of biomedical applications, e.g., magnetic hyperthermia, drug delivery, tissue engineering, and neuromodulation. In this work, this type of hydrogel has been fabricated from hyaluronan (HA) filled with a binary system of Al₂O₃ nanoparticles and multicore magnetic particles (MCPs), which were obtained by clustering of superparamagnetic iron oxide FeO_<i>x</i> NPs. It was established that the presence of diamagnetic Al₂O₃ has several positive effects: it enhances the hydrogel storage modulus and long-term stability in the cell cultivation medium; prevents the magnetic interaction among the MCPs. The HA hydrogel provides rapid heating of 0.3 °C per min under exposure to low amplitude radio frequency alternating magnetic field. Furthermore, the magneto-responsive hydrogel was successfully used to encapsulate cells and extrusion-based 3D printing with 87±6% cell viability, thus providing a bio-ink. The combination of high heating efficiency, softness, cytocompatibility, and 3D printability of magnetic HA hydrogel leads to a material suitable for biomedical applications.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10221818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photothermal therapy using graphene quantum dots.","authors":"Mohammad Suhaan Dar,&nbsp;Tanveer A Tabish,&nbsp;Nanasaheb D Thorat,&nbsp;G Swati,&nbsp;Niroj Kumar Sahu","doi":"10.1063/5.0160324","DOIUrl":"https://doi.org/10.1063/5.0160324","url":null,"abstract":"<p><p>The rapid development of powerful anti-oncology medicines have been possible because of advances in nanomedicine. Photothermal therapy (PTT) is a type of treatment wherein nanomaterials absorb the laser energy and convert it into localized heat, thereby causing apoptosis and tumor eradication. PTT is more precise, less hazardous, and easy-to-control in comparison to other interventions such as chemotherapy, photodynamic therapy, and radiation therapy. Over the past decade, various nanomaterials for PTT applications have been reviewed; however, a comprehensive study of graphene quantum dots (GQDs) has been scantly reported. GQDs have received huge attention in healthcare technologies owing to their various excellent properties, such as high water solubility, chemical stability, good biocompatibility, and low toxicity. Motivated by the fascinating scientific discoveries and promising contributions of GQDs to the field of biomedicine, we present a comprehensive overview of recent progress in GQDs for PTT. This review summarizes the properties and synthesis strategies of GQDs including top-down and bottom-up approaches followed by their applications in PTT (alone and in combination with other treatment modalities such as chemotherapy, photodynamic therapy, immunotherapy, and radiotherapy). Furthermore, we also focus on the systematic study of <i>in vitro</i> and <i>in vivo</i> toxicities of GQDs triggered by PTT. Moreover, an overview of PTT along with the synergetic application used with GQDs for tumor eradication are discussed in detail. Finally, directions, possibilities, and limitations are described to encourage more research, which will lead to new treatments and better health care and bring people closer to the peak of human well-being.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10444203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10056739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnetic self-assembly of 3D multicellular microscaffolds: A biomimetic brain tumor-on-a-chip for drug delivery and selectivity testing.","authors":"Attilio Marino,&nbsp;Matteo Battaglini,&nbsp;Alessio Carmignani,&nbsp;Francesca Pignatelli,&nbsp;Daniele De Pasquale,&nbsp;Omar Tricinci,&nbsp;Gianni Ciofani","doi":"10.1063/5.0155037","DOIUrl":"https://doi.org/10.1063/5.0155037","url":null,"abstract":"<p><p>In recent years, the need for highly predictive brain cancer models to test new anticancer compounds and experimental therapeutic approaches has significantly increased. Realistic <i>in vitro</i> brain tumor-on-a-chip platforms would allow a more accurate selection of valid candidate drugs and nanomedicines, therefore alleviating the economic and ethical issues of unsuccessful studies <i>in vivo</i>. Here, we present a multi-functional self-assembled brain tumor-on-a-chip model characterized by 3D glioma cultures interfaced both to nonmalignant brain cells of the peritumoral niche and to a 3D-real-scale blood-brain barrier (BBB) microfluidic system. This platform allowed us to screen multiple features, such as BBB crossing capabilities, apoptotic efficacy against GBM cells, and side effects on nonmalignant brain cells of a promising anticancer drug, nutlin-3a, which is fundamental for the treatment of brain cancer.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10375466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10056161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oscillatory shear stress-induced downregulation of TET1s injures vascular endothelial planar cell polarity by suppression of actin polymerization.","authors":"Kai Qu,&nbsp;Caihong Wang,&nbsp;Lu Huang,&nbsp;Xian Qin,&nbsp;Kun Zhang,&nbsp;Juhui Qiu,&nbsp;Guixue Wang","doi":"10.1063/5.0141289","DOIUrl":"https://doi.org/10.1063/5.0141289","url":null,"abstract":"<p><p>Vascular endothelial polarity induced by blood flow plays crucial roles in the development of atherosclerosis. Loss of endothelial polarity leads to an increase in permeability and leukocyte recruitment, which are crucial hallmarks of atherosclerotic initiation. Endothelial cells exhibit a morphological adaptation to hemodynamic shear stress and possesses planar cell polarity to the direction of blood flow. However, the mechanism of how hemodynamic shear stress regulates endothelial planar cell polarity has not been firmly established. Here, we found that TET1s, a short isoform of Tet methylcytosine dioxygenase 1, was a mediator in the regulation of the planar cell polarity in endothelial cells in response to hemodynamic shear stress. In the process, low expression of TET1s induced by oscillatory shear stress led to the endothelial planar polarity damage through inhibition of F-actin polymerization. TET1s can regulate demethylation level of the sFRP-1 promoter to alter the expression of sFRP-1, which affects the interaction of sFRP-1/Fzd4 and F-actin polymerization. Our study revealed the mechanism of how TET1s mediates endothelial planar cell polarity in response to hemodynamic shear stress and provides a new insight for the prevention of atherosclerosis.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9932988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemodynamics of thrombus formation in intracranial aneurysms: An <i>in silico</i> observational study.","authors":"Qiongyao Liu,&nbsp;Ali Sarrami-Foroushani,&nbsp;Yongxing Wang,&nbsp;Michael MacRaild,&nbsp;Christopher Kelly,&nbsp;Fengming Lin,&nbsp;Yan Xia,&nbsp;Shuang Song,&nbsp;Nishant Ravikumar,&nbsp;Tufail Patankar,&nbsp;Zeike A Taylor,&nbsp;Toni Lassila,&nbsp;Alejandro F Frangi","doi":"10.1063/5.0144848","DOIUrl":"https://doi.org/10.1063/5.0144848","url":null,"abstract":"<p><p>How prevalent is spontaneous thrombosis in a population containing all sizes of intracranial aneurysms? How can we calibrate computational models of thrombosis based on published data? How does spontaneous thrombosis differ in normo- and hypertensive subjects? We address the first question through a thorough analysis of published datasets that provide spontaneous thrombosis rates across different aneurysm characteristics. This analysis provides data for a subgroup of the general population of aneurysms, namely, those of large and giant size (>10 mm). Based on these observed spontaneous thrombosis rates, our computational modeling platform enables the first <i>in silico</i> observational study of spontaneous thrombosis prevalence across a broader set of aneurysm phenotypes. We generate 109 virtual patients and use a novel approach to calibrate two trigger thresholds: residence time and shear rate, thus addressing the second question. We then address the third question by utilizing this calibrated model to provide new insight into the effects of hypertension on spontaneous thrombosis. We demonstrate how a mechanistic thrombosis model calibrated on an intracranial aneurysm cohort can help estimate spontaneous thrombosis prevalence in a broader aneurysm population. This study is enabled through a fully automatic multi-scale modeling pipeline. We use the clinical spontaneous thrombosis data as an indirect population-level validation of a complex computational modeling framework. Furthermore, our framework allows exploration of the influence of hypertension in spontaneous thrombosis. This lays the foundation for <i>in silico</i> clinical trials of cerebrovascular devices in high-risk populations, e.g., assessing the performance of flow diverters in aneurysms for hypertensive patients.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10329514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9814114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging trends in the development of flexible optrode arrays for electrophysiology.","authors":"Reem M Almasri,&nbsp;François Ladouceur,&nbsp;Damia Mawad,&nbsp;Dorna Esrafilzadeh,&nbsp;Josiah Firth,&nbsp;Torsten Lehmann,&nbsp;Laura A Poole-Warren,&nbsp;Nigel H Lovell,&nbsp;Amr Al Abed","doi":"10.1063/5.0153753","DOIUrl":"https://doi.org/10.1063/5.0153753","url":null,"abstract":"<p><p>Optical-electrode (optrode) arrays use light to modulate excitable biological tissues and/or transduce bioelectrical signals into the optical domain. Light offers several advantages over electrical wiring, including the ability to encode multiple data channels within a single beam. This approach is at the forefront of innovation aimed at increasing spatial resolution and channel count in multichannel electrophysiology systems. This review presents an overview of devices and material systems that utilize light for electrophysiology recording and stimulation. The work focuses on the current and emerging methods and their applications, and provides a detailed discussion of the design and fabrication of flexible arrayed devices. Optrode arrays feature components non-existent in conventional multi-electrode arrays, such as waveguides, optical circuitry, light-emitting diodes, and optoelectronic and light-sensitive functional materials, packaged in planar, penetrating, or endoscopic forms. Often these are combined with dielectric and conductive structures and, less frequently, with multi-functional sensors. While creating flexible optrode arrays is feasible and necessary to minimize tissue-device mechanical mismatch, key factors must be considered for regulatory approval and clinical use. These include the biocompatibility of optical and photonic components. Additionally, material selection should match the operating wavelength of the specific electrophysiology application, minimizing light scattering and optical losses under physiologically induced stresses and strains. Flexible and soft variants of traditionally rigid photonic circuitry for passive optical multiplexing should be developed to advance the field. We evaluate fabrication techniques against these requirements. We foresee a future whereby established telecommunications techniques are engineered into flexible optrode arrays to enable unprecedented large-scale high-resolution electrophysiology systems.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10222485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}